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Biomaterials, Feb 04 2025, 318 S0142-9612(25)00084-5 | https://doi.org/10.1016/j.biomaterials.2025.123165 Glycoengineered stem cell-derived extracellular vesicles for targeted therapy of acute kidney injury

So Hee Kim ^a,1, Chan Ho Kim ^a,1, Chang Hyun Lee ^a, Jungmi Lee^a, Heegun Kang ^a, Sohyun Cho ^b, Won Ho Jang^a, Minsung Park^c, Minji Ha ^a, Jiyeon Kim ^b, Wooram Um ^d, Seunglee Kwon ^a, Sangho Lee ^e, Jin Woong Kim ^a, Chan-Hwa Chung ^a, Jae Hyung Park ^a,b,c

^aSchool of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea
^bDepartment of MetaBioHealth, SKKU Institute for Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea
^cDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
^dDepartment of Biotechnology, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea
^eDepartment of Biological Sciences, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Republic of Korea Suwon, Suwon, 16419, Republic of Korea

¹These authors contributed equally to this work.
Corresponding author : Jae Hyung Park

Abstract

Acute kidney injury (AKI) is associated with high morbidity and mortality rates, primarily due to the lack of effective therapeutic options for kidney repair. To restore the biological function of injured kidney, there is a need to protect renal tubular epithelial cells (RTECs) and regulate M1 macrophages, responsible for progress of AKI. Herein, based on metabolic glycoengineering-mediated click chemistry, we prepare the engineered extracellular vesicles (pSEVs), derived from PEGylated hyaluronic acid (HA)-modified mesenchymal stem cells. Owing to their cell-protective and anti-inflammatory properties, pSEVs effectively prevent the apoptosis of RTECs and inhibit the polarization of macrophages into an inflammatory phenotype in vitro. When systemically administered into the cisplatin-induced AKI animal model, pSEVs selectively accumulate in injured kidneys via HA-mediated binding to CD44 and toll-like receptor4 which are over-expressed on RTECs and M1 macrophages, respectively. This targeted delivery efficiently alleviates AKI-related symptoms, as evidenced by delayed kidney weight reduction, and decreased levels of creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin. Overall, pSEVs show potent anti-inflammatory effects and specific targeting to injured kidneys, presenting a considerable potential as the therapeutics for AKI.

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형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-27)
연구진국내 연구진
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